Terminal differentiation of mammalian epidermal keratinocytes eventually creates a keratin filament matrix encased within a sheet of covalently cross-linked proteins called the cornified cell envelope (CE). Biogenesis of the CE is being studied in both normal and diseased states, e.g. psoriasis. - STEM measurements of mass/area on purified CEs allow one to evaluate their homogeneity and test for possible specialized areas within a given CE. CEs isolated from human epidermis (normal and psoriatic), mouse epidermis (normal and transgenic), other epithelia, and cultured keratinocytes are being studied. Several different methods of preparation have been examined since residual detergent between the CE's and the carbon substrate can affect mass measurements. The average thickness and mass/area of the mature envelopes are amazingly the same regardless of the tissue. Tliese results are helping to define the current model of CE assembly.